Tomudex is a specific inhibitor of thymidylate synthease with clinical activity in colorectal cancer. We have demonstrated in vitro synergism between Tomudex (TOM) and IdUrd, a cytotoxic pyrimidine analog, against colon and bladder human carcinoma cell lines as well as increased IdUrd incorporation into DNA. We designed a phase I trial to determine the MTD, pharmacokinetics and biologic effects of escalating doses of the combination, with the IdUrd given as a 24 hour infusion after a TOM 15 minute infusion.